The genetic basis of disease induction by murine leukemia viruses (MuLVs) has been studied largely by analysis of the different inbred strains of the laboratory mouse. However, wild mice show a greater genetic diversity than the inbred strains, and our use of these animals has expanded our understanding of viral leukemogenesis in several important ways. First, direct analysis of wild mice shows that they differ markedly from the inbred strains n the number and type of endogenous MuLVs they carry. We have now shown that xenotropic and MCF-related MuLV env genes are present as endogenous copies in different populations of wild mice. We have also shown that amphotropic MuLVs are transmitted as exogenous virus in Southern California mice and are not present as germline copies in any mammalian DNA tested. Second, infectious viruses from wild mice differ from their laboratory mouse counterparts at the molecular level and have different patterns of pathogenesis. Transcription of endogenous MuLV sequences has been examined in various mild mice, and a new MuLV isolate, HoMuLV, has been shown to be leukemogenic in inbred strains.